International Journal of Neonatal Screening

9 pages, 211 KiB

Open AccessArticle

Family Perspectives on Newborn Screening for X-Linked Adrenoleukodystrophy in California

by Katharina Schwan, Janey Youngblom, Kara Weisiger, Jessica Kianmahd, Rebecca Waggoner and Joanna Fanos

Int. J. Neonatal Screen. 2019, 5(4), 42; https://doi.org/10.3390/ijns5040042 - 13 Nov 2019

Cited by 20 | Viewed by 3778

Abstract

X-linked adrenoleukodystrophy (ALD) is caused by gene variants in the ABCD1 gene, resulting in a varied clinical spectrum. Males with ALD present with symptoms ranging from isolated adrenal insufficiency and slowly progressive myelopathy to severe cerebral demyelination. Females who are heterozygous for ALD [...] Read more.

X-linked adrenoleukodystrophy (ALD) is caused by gene variants in the ABCD1 gene, resulting in a varied clinical spectrum. Males with ALD present with symptoms ranging from isolated adrenal insufficiency and slowly progressive myelopathy to severe cerebral demyelination. Females who are heterozygous for ALD typically develop milder symptoms by late adulthood. Treatment for adrenal insufficiency associated with ALD exists in the form of cortisol, and cerebral ALD may be treated with stem cell transplantation. Currently, there is no treatment for myelopathy. Since 2013, at least 14 states have added ALD to their newborn screening (NBS) panel, including California in 2016. We examined the impact of a positive NBS result for ALD on families in California. Qualitative interviews were conducted with mothers of 10 children who were identified via NBS for ALD. Interviews were transcribed verbatim and analyzed using thematic analysis by two coders. Mothers felt strongly that ALD should be included on California’s NBS panel; however, many expressed concerns over their experience. Themes included stress at initial phone call, difficulty living with uncertainty, concerns regarding mental health support, and desire for more information on disease progression, treatments and clinical trials. Mothers exhibited diverse coping strategies, including relying on faith, information seeking, and maintaining hope. Mothers’ recommendations for healthcare providers included: educating providers making the initial phone call, providing patient-friendly resources, offering information about ongoing research, and streamlining care coordination. Advice for parents of children with ALD focused on staying hopeful and appreciating the time they have with their children. As more states add ALD to their NBS panel, it is important to improve the current model to promote family resiliency and autonomy. Full article

13 pages, 2188 KiB

Open AccessArticle

A Novel System for Spinal Muscular Atrophy Screening in Newborns: Japanese Pilot Study

by Masakazu Shinohara, Emma Tabe Eko Niba, Yogik Onky Silvana Wijaya, Izumi Takayama, Chisako Mitsuishi, Sakae Kumasaka, Yoichi Kondo, Akihiro Takatera, Isamu Hokuto, Ichiro Morioka, Kazutaka Ogiwara, Kimimasa Tobita, Atsuko Takeuchi, Hisahide Nishio and for the SMA-NBS PILOT STUDY GROUP

Int. J. Neonatal Screen. 2019, 5(4), 41; https://doi.org/10.3390/ijns5040041 - 12 Nov 2019

Cited by 24 | Viewed by 6940

Abstract

Spinal muscular atrophy (SMA) is a neuromuscular disorder caused by SMN1 gene deletion/mutation. The drug nusinersen modifies SMN2 mRNA splicing, increasing the production of the full-length SMN protein. Recent studies have demonstrated the beneficial effects of nusinersen in patients with SMA, particularly when [...] Read more.

Spinal muscular atrophy (SMA) is a neuromuscular disorder caused by SMN1 gene deletion/mutation. The drug nusinersen modifies SMN2 mRNA splicing, increasing the production of the full-length SMN protein. Recent studies have demonstrated the beneficial effects of nusinersen in patients with SMA, particularly when treated in early infancy. Because nusinersen treatment can alter disease trajectory, there is a strong rationale for newborn screening. In the current study, we validated the accuracy of a new system for detecting SMN1 deletion (Japanese patent application No. 2017-196967, PCT/JP2018/37732) using dried blood spots (DBS) from 50 patients with genetically confirmed SMA and 50 controls. Our system consists of two steps: (1) targeted pre-amplification of SMN genes by direct polymerase chain reaction (PCR) and (2) detection of SMN1 deletion by real-time modified competitive oligonucleotide priming-PCR (mCOP-PCR) using the pre-amplified products. Compared with PCR analysis results of freshly collected blood samples, our system exhibited a sensitivity of 1.00 (95% confidence interval [CI] 0.96–1.00) and a specificity of 1.00 (95% CI 0.96–1.00). We also conducted a prospective SMA screening study using DBS from 4157 Japanese newborns. All DBS tested negative, and there were no screening failures. Our results indicate that the new system can be reliably used in SMA newborn screening. Full article

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15 pages, 1543 KiB

Open AccessArticle

Next Generation Sequencing in Newborn Screening in the United Kingdom National Health Service

by Julia C. van Campen, Elizabeth S. A. Sollars, Rebecca C. Thomas, Clare M. Bartlett, Antonio Milano, Matthew D. Parker, Jennifer Dawe, Peter R. Winship, Gerrard Peck, Darren Grafham, Richard J. Kirk, James R. Bonham, Anne C. Goodeve and Ann Dalton

Int. J. Neonatal Screen. 2019, 5(4), 40; https://doi.org/10.3390/ijns5040040 - 5 Nov 2019

Cited by 26 | Viewed by 7544

Abstract

Next generation DNA sequencing (NGS) has the potential to improve the diagnostic and prognostic utility of newborn screening programmes. This study assesses the feasibility of automating NGS on dried blood spot (DBS) DNA in a United Kingdom National Health Service (UK NHS) laboratory. [...] Read more.

Next generation DNA sequencing (NGS) has the potential to improve the diagnostic and prognostic utility of newborn screening programmes. This study assesses the feasibility of automating NGS on dried blood spot (DBS) DNA in a United Kingdom National Health Service (UK NHS) laboratory. An NGS panel targeting the entire coding sequence of five genes relevant to disorders currently screened for in newborns in the UK was validated on DBS DNA. An automated process for DNA extraction, NGS and bioinformatics analysis was developed. The process was tested on DBS to determine feasibility, turnaround time and cost. The analytical sensitivity of the assay was 100% and analytical specificity was 99.96%, with a mean 99.5% concordance of variant calls between DBS and venous blood samples in regions with ≥30× coverage (96.8% across all regions; all variant calls were single nucleotide variants (SNVs), with indel performance not assessed). The pipeline enabled processing of up to 1000 samples a week with a turnaround time of four days from receipt of sample to reporting. This study concluded that it is feasible to automate targeted NGS on routine DBS samples in a UK NHS laboratory setting, but it may not currently be cost effective as a first line test. Full article

(This article belongs to the Special Issue Selected Papers from 10th ISNS International Symposium/11th Asia Pacific Regional Meeting)

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11 pages, 941 KiB

Open AccessArticle

Development of a Multiplex Real-Time PCR Assay for the Newborn Screening of SCID, SMA, and XLA

by Cristina Gutierrez-Mateo, Anne Timonen, Katja Vaahtera, Markku Jaakkola, David M Hougaard, Jonas Bybjerg-Grauholm, Marie Baekvad-Hansen, Dea Adamsen, Galina Filippov, Stephanie Dallaire, David Goldfarb, Daniel Schoener and Rongcong Wu

Int. J. Neonatal Screen. 2019, 5(4), 39; https://doi.org/10.3390/ijns5040039 - 2 Nov 2019

Cited by 27 | Viewed by 7914

Abstract

Numerous studies have shown evidence supporting the benefits of universal newborn screening for primary immunodeficiencies (PID) and for Spinal Muscular Atrophy (SMA). We have developed a four-plex, real-time PCR assay to screen for Severe Combined Immune Deficiencies (SCID), X-linked agammaglobulinemia (XLA), and SMA [...] Read more.

Numerous studies have shown evidence supporting the benefits of universal newborn screening for primary immunodeficiencies (PID) and for Spinal Muscular Atrophy (SMA). We have developed a four-plex, real-time PCR assay to screen for Severe Combined Immune Deficiencies (SCID), X-linked agammaglobulinemia (XLA), and SMA in DNA extracted from a single 3.2 mm punch of a dried blood spot (DBS). A simple, high-throughput, semi-automated DNA extraction method was developed for a Janus liquid handler that can process 384 DBS punches in four 96-well plates in just over one hour with sample tracking capability. The PCR assay identifies the absence of exon 7 in the SMN1 gene, while simultaneously evaluating the copy number of T-cell receptor excision circles (TREC) and Kappa-deleting recombination excision circles (KREC) molecules. Additionally, the amplification of a reference gene, RPP30, was included in the assay as a quality/quantity indicator of DNA isolated from the DBS. The assay performance was demonstrated on over 3000 DNA samples isolated from punches of putative normal newborn DBS. The reliability and analytical accuracy were further evaluated using DBS controls, and contrived and confirmed positive samples. The results from this study demonstrate the potential of future molecular DBS assays, and highlight how a multiplex assay could benefit newborn screening programs. Full article

(This article belongs to the Special Issue Selected Papers from 11th ISNS European Regional Meeting)

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7 pages, 1048 KiB

Open AccessArticle

Incidence of Glucose-6-Phosphate Dehydrogenase Deficiency among Swedish Newborn Infants

by Annika Ohlsson, Katarina Rehnholm, Kumar Shubham and Ulrika von Döbeln

Int. J. Neonatal Screen. 2019, 5(4), 38; https://doi.org/10.3390/ijns5040038 - 29 Oct 2019

Cited by 5 | Viewed by 3203

Abstract

Sweden has 10.2 million inhabitants and more than 2.4 million have a foreign background. A substantial number of immigrants come from countries where glucose-6-phosphate dehydrogenase deficiency (G6PDD) is frequent. The total birth rate annually in Sweden is approximately 117,000 and newborn screening is [...] Read more.

Sweden has 10.2 million inhabitants and more than 2.4 million have a foreign background. A substantial number of immigrants come from countries where glucose-6-phosphate dehydrogenase deficiency (G6PDD) is frequent. The total birth rate annually in Sweden is approximately 117,000 and newborn screening is centralized to one laboratory. We determined glucose-6-phosphate dehydrogenase (G6PD) activity in 10,098 dried blood spot samples (DBS) from the whole country with a fluorometric assay (LabSystems Diagnostics Oy, Finland). The first 5451 samples were anonymised and run as singletons, whilst the following 4647 samples were coded. Enzyme activity ≤40% of the mean of the day was found in 58 samples (1/170) and among these, 29 had activities ≤10% (1/350). Twenty-nine samples with residual activities between 2–39% in the coded cohort were subjected to Sanger sequencing. Disease-causing variants were identified in 26 out of 29 infants, of which six were girls. In three patients, we did not find any disease-causing variants, although two patients were hemizygous for the known polymorphisms c.1311T>C and c.1365-13C>T. The most common disease-causing variant found in 15 of the 29 samples (12 hemizygotes, two heterozygotes, one homozygote) was the Mediterranean mutation, c.563C>T (p.(Ser188Phe)) in exon 6. G6PDD is thus a surprisingly prevalent disorder in Sweden. Full article

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9 pages, 1444 KiB

Open AccessReview

Newborn Screening: Current Status in Alberta, Canada

by Andy De Souza, Vanessa Wolan, Angie Battochio, Susan Christian, Stacey Hume, Grace Johner, Margaret Lilley, Ross Ridsdale, Kareena Schnabl, Chi Tran, Jolene Yuen-Jung and Iveta Sosova

Int. J. Neonatal Screen. 2019, 5(4), 37; https://doi.org/10.3390/ijns5040037 - 1 Oct 2019

Cited by 11 | Viewed by 6202

Abstract

Newborn screening (NBS) in Alberta is delivered by a number of government and health service entities who work together to provide newborn screening to infants born in Alberta, the Northwest Territories, and the Kitikmeot region of the Nunavut territory. The Alberta panel screens [...] Read more.

Newborn screening (NBS) in Alberta is delivered by a number of government and health service entities who work together to provide newborn screening to infants born in Alberta, the Northwest Territories, and the Kitikmeot region of the Nunavut territory. The Alberta panel screens for 21 disorders (16 metabolic, two endocrine, cystic fibrosis, severe combined immunodeficiency, and sickle cell disease). NBS is a standard of care, but is not mandatory. NBS performance is monitored by the Alberta Newborn Metabolic Screening (NMS) Program and NMS Laboratory, who strive for continuous quality improvement. Performance analysis found that over 99% of registered infants in Alberta received a newborn screen and over 98% of these infants received a screen result within 10 days of age. Full article

(This article belongs to the Special Issue Selected Papers from 11th ISNS European Regional Meeting)

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2 pages, 182 KiB

Open AccessEditorial

Editorial for Special Issue “Newborn Screening for Sickle Cell Disease and other Haemoglobinopathies”

by Raffaella Colombatti, Elena Cela, Jacques Elion and Stephan Lobitz

Int. J. Neonatal Screen. 2019, 5(4), 36; https://doi.org/10.3390/ijns5040036 - 20 Sep 2019

Cited by 3 | Viewed by 2154

Abstract

Sickle cell disease (SCD) is among the most common genetic disorders in the world, affecting over 300,000 newborns annually, with estimates for further increases to over 400,000 annual births within the next generation and with a wider geographical distribution of affected individuals due [...] Read more.

Sickle cell disease (SCD) is among the most common genetic disorders in the world, affecting over 300,000 newborns annually, with estimates for further increases to over 400,000 annual births within the next generation and with a wider geographical distribution of affected individuals due to global migration [...] Full article

(This article belongs to the Special Issue Newborn Screening for Sickle Cell Disease and other Haemoglobinopathies)

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Int. J. Neonatal Screen., Volume 5, Issue 4 (December 2019) – 7 articles

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